SpadaHC: a database to improve the classification of variants in hereditary cancer genes in the Spanish population.

Accurate classification of genetic variants is crucial for clinical decision-making in hereditary cancer. In Spain, genetic diagnostic laboratories have traditionally approached this task independently due to the lack of a dedicated resource. Here we present SpadaHC, a web-based database for sharing variants in hereditary cancer genes in the Spanish population. SpadaHC is implemented using a three-tier architecture consisting of a relational database, a web tool and a bioinformatics pipeline. Contributing laboratories can share variant classifications and variants from individuals in Variant Calling Format (VCF) format. The platform supports open and restricted access, flexible dataset submissions, automatic pseudo-anonymization, VCF quality control, variant normalization and liftover between genome builds. Users can flexibly explore and search data, receive automatic discrepancy notifications and access SpadaHC population frequencies based on many criteria. In February 2024, SpadaHC included 18 laboratory members, storing 1.17 million variants from 4306 patients and 16 343 laboratory classifications. In the first analysis of the shared data, we identified 84 genetic variants with clinically relevant discrepancies in their classifications and addressed them through a three-phase resolution strategy. This work highlights the importance of data sharing to promote consistency in variant classifications among laboratories, so patients and family members can benefit from more accurate clinical management. Database URL: https://spadahc.ciberisciii.es/.

Concepciones de usuarios sobre nuevas vías de administración de profilaxis pre-exposición para el VIH / Users' expectations of the new pre-exposure prophylaxis for the HIV modalities

Resumen Este artículo tiene como objetivo discutir las concepciones de los Hombres Gay, Hombres Bisexuales y una Mujer Transgénero que usan o quieren usar profilaxis previa a la exposición por el virus de la inmunodeficiencia humana oral (PrEP) sobre nuevas vías de administración. Fueron entrevistados 17 usuarios del BCN Checkpoint. Las entrevistas fueron grabadas en audio, sometidas a análisis categorial temático teniendo en cuenta la perspectiva praxeográfica. Todos están adaptados al uso de la PrEP diaria y a demanda. En relación con las nuevas vías de administración (PrEP inyección intramuscular cada dos meses; pastilla mensual; inyección subcutánea cada seis meses) todos son muy receptivos a esas posibilidades, pero les falta información sobre las especificidades de cada una de ellas y una evaluación específica de sus necesidades. Tanto la satisfacción con el uso de PrEP oral, como las expectativas sobre las nuevas vías de administración son positivas. Sin embargo, lo más importante para los/a entrevistados/a es la garantía de que tendrán seguimiento para continuar cuidando de la salud afectivo-sexual, lo que no depende del tipo de vía de administración.

Abstract This article aims to discuss the expectations of Homosexual Men, Bisexual Men and a Transgender Woman, who use or want to use an oral pre-exposure prophylaxis (PrEP) for the human immunodeficiency virus (HIV) about PrEP modalities. Sixteen PrEP users, who are followed up in the BCN Checkpoint, were interviewed,. The interviews were audio-recorded, subjected to thematic categorical analysis within the theoretical framework from the praxiographic perspective. They are all adapted to the use of daily oral and event-based PrEP. In relation to the new PrEP modalities (monthly pill; intramuscular injection every two months; subcutaneous injection every six months), they are all very receptive to these possibilities, but they lack information on the specificities of each and specific assessment of their needs. Comments about the use of oral PrEP are positive, and expectations regarding the new PrEP modalities are visibly high. However, the most important thing for the interviewees is the guarantee that they will have follow-up appointments to continue taking care of their affective-sexual health, which is not dependent on the type of PrEP modalities.

High Body Mass Index and Response to Anti-Tumor Necrosis Factor Therapy in Pediatric Crohn's Disease.

INTRODUCTION: Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI). METHODS: The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined. RESULTS: Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 µg/mL, P = 0.02). IFX trough levels did not differ between BMI groups. DISCUSSION: Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.

Photoprotective effect of topical treatment with Lopezia racemosa extract against deleterious UVB irradiation effects in the skin of hairless mice.

Lopezia racemosa is known as a "mosquito flower or perlilla." It is commonly found in corn crops. In traditional Mexican medicine, this plant is used to treat stomach cancer and urinary tract infections. Likewise, compounds and extracts isolated from plants have shown cytotoxic and anti-inflammatory effects. The objective of this study was to evaluate the photochemoprotective effect of topical treatment with the methanolic extract of L. racemosa (MELR) as a photochemoprotective agent against the harmful effects of UV irradiation (UVR) on a bacterial model and hairless mice. The MELR components were separated and analyzed via HPLC-UV-ESI-MS. Antioxidant activity was evaluated by the ability of MERL to scavenge DPPH and ABTS free radicals and by its FRAP capacity. The toxicity of MELR was evaluated in keratinocyte cultures. The photoprotective capacity of MELR was assessed through challenge experiments using models with bacteria and hairless CD1 et/et mice; cytokines related to the damage caused by UVR were also measured. In the methanolic extract of L. racemosa, five metabolites were detected and identified: two isomers of quercetin 6-C glycoside, orientin, quercetin 3-(6″-acetylglycoside) and quercetin 3-(6″-galloylglycoside) 7-(2,3-dihydroxytetrahydro-2H-pyran-4-yl acetate). MELR exhibited DPPH and ABTS radical scavenging properties, in addition to Fe ion reducing activity. MELR showed a photoprotective effect against UVB radiation-induced death in Escherichia coli bacteria. At the histological level, topical treatment of CD-1 et/et mice with MERL reduced the damage caused by UVR. Quantification of interleukins in the blood of mice revealed that the expression of IL-12 was greater in the control group treated with ultraviolet radiation than in the group protected with MELR. The methanolic extract of L. racemosa has photochemoprotective properties.

Perioperative nutrition in the setting of pediatric inflammatory bowel disease.

BACKGROUND: Optimization of nutrition prior to inflammatory bowel disease (IBD)-related surgery could improve outcomes. The aim of this study was to assess the perioperative nutrition status and management of children undergoing intestinal resection for treatment of their IBD. METHODS: We identified all patients with IBD who underwent primary intestinal resection. We identified malnutrition using established criteria and methods of nutrition provision at various time points (preoperative outpatient evaluation, admission, and postoperative outpatient follow-up) for elective cases (who underwent their procedure at a scheduled admission) and urgent cases (who underwent an unplanned surgical intervention). We also recorded data on postsurgical complications. RESULTS: A total of 84 patients were identified in this single-center study (male sex: 40%, mean age: 14.5 years, Crohn's disease: 65%). Thirty-four patients (40%) had some degree of malnutrition. Prevalence of malnutrition in the urgent and elective cohorts was similar (48% vs 36%; P = 0.37). Of these patients, 29 (34%) were noted to be on some type of nutrition supplementation prior to surgery. Postoperatively, BMI z scores increased (-0.61 vs -0.42; P = 0.0008), but the percentage of patients who were malnourished did not change from preoperative status (40% vs 40%; P = 0.10). Despite this, use of nutrition supplementation was only noted in 15 (17%) patients at postoperative follow-up. Complications were not associated with nutrition status. CONCLUSION: Utilization of supplemental nutrition decreased postprocedure despite no change in malnutrition prevalence. These findings support the development of a pediatric-specific perioperative nutrition protocol in the setting of IBD-related surgery.

Hypereosinophilic Syndrome with Pulmonary Involvement in Ulcerative Colitis.

Reactive eosinophilia is associated with inflammatory bowel disease and is more common in patients with ulcerative colitis (UC) compared with Crohn's disease. The prevalence rate of peripheral blood eosinophilia in patients with inflammatory bowel disease has been described to be as high as 30%-40% of patients in a pediatric study. The coexistence of hypereosinophilic syndrome (HES) and UC is uncommon. We present a 15-year-old boy with UC associated with HES who presented with chest pain and shortness of breath. Laboratory evaluation showed marked eosinophilia. Alternative causes of eosinophilia including eosinophilic leukemia, infections, or drug-induced eosinophilic pneumonia were ruled out. The patient was ultimately diagnosed with HES responsive to mepolizumab.

vaRHC: an R package for semi-automation of variant classification in hereditary cancer genes according to ACMG/AMP and gene-specific ClinGen guidelines.

MOTIVATION: Germline variant classification allows accurate genetic diagnosis and risk assessment. However, it is a tedious iterative process integrating information from several sources and types of evidence. It should follow gene-specific (if available) or general updated international guidelines. Thus, it is the main burden of the incorporation of next-generation sequencing into the clinical setting. RESULTS: We created the vaRiants in HC (vaRHC) R package to assist the process of variant classification in hereditary cancer by: (i) collecting information from diverse databases; (ii) assigning or denying different types of evidence according to updated American College of Molecular Genetics and Genomics/Association of Molecular Pathologist gene-specific criteria for ATM, CDH1, CHEK2, MLH1, MSH2, MSH6, PMS2, PTEN, and TP53 and general criteria for other genes; (iii) providing an automated classification of variants using a Bayesian metastructure and considering CanVIG-UK recommendations; and (iv) optionally printing the output to an .xlsx file. A validation using 659 classified variants demonstrated the robustness of vaRHC, presenting a better criteria assignment than Cancer SIGVAR, an available similar tool. AVAILABILITY AND IMPLEMENTATION: The source code can be consulted in the GitHub repository (https://github.com/emunte/vaRHC) Additionally, it will be submitted to CRAN soon.

Evaluating the Accuracy of Self-Collected Swabs for the Diagnosis of Mpox.

We evaluated the accuracy of patient-collected skin lesions, oropharyngeal, and rectal swabs among 50 individuals enrolled in a study of mpox viral dynamics. We found that the performance of self-collected samples was similar to that of physician-collected samples, suggesting that self-sampling is a reliable strategy for diagnosing mpox.

Priorities in Cardio-Oncology Basic and Translational Science: GCOS 2023 Symposium Proceedings: JACC: CardioOncology State-of-the-Art Review.

Despite improvements in cancer survival, cancer therapy-related cardiovascular toxicity has risen to become a prominent clinical challenge. This has led to the growth of the burgeoning field of cardio-oncology, which aims to advance the cardiovascular health of cancer patients and survivors, through actionable and translatable science. In these Global Cardio-Oncology Symposium 2023 scientific symposium proceedings, we present a focused review on the mechanisms that contribute to common cardiovascular toxicities discussed at this meeting, the ongoing international collaborative efforts to improve patient outcomes, and the bidirectional challenges of translating basic research to clinical care. We acknowledge that there are many additional therapies that are of significance but were not topics of discussion at this symposium. We hope that through this symposium-based review we can highlight the knowledge gaps and clinical priorities to inform the design of future studies that aim to prevent and mitigate cardiovascular disease in cancer patients and survivors.

Acute Vocal Fold Hemorrhage: Retrospective Analysis in a Voice Unit.

OBJECTIVES: To describe our experience in diagnosis, evaluation, management and evolution of adult patients diagnosed with vocal fold hemorrhage (VFH) in the Voice Unit at Universidad Católica Clinical Hospital Santiago, Chile. STUDY DESIGN: Retrospective chart review. METHODS: Adult patients diagnosed with VFH between 2012 and 2020 were included. Demographic data, medical and vocal history, vocal symptoms and questionnaires, laryngeal videostroboscopy, treatment, and follow-up controls were reviewed. RESULTS: A total of 34 patients were included, 52.9% (18) patients were female and 47.1% (16) male. Mean age was 42 years (22-76 years) and 47.1% were professional voice users. Principal voice symptoms were dysphonia (32/34), vocal fatigue (21/34) and throat clearing (17/34). Twenty-six (76.5%) patients had VFH and a concomitant lesion in the same vocal fold (VF), being a hemorrhagic polyp the most prevalent associated lesion (61.8%). All patients were managed initially with voice rest, showing improvement at first follow up visit according to VRQOL-STD (mean difference -32.43, P = 0.009) and VHI-10 (mean difference 11.22, P = 0.036), and laryngeal videostroboscopic resolution in 66.7% (8/12) at a mean 12.5 (range 6-30) days. CONCLUSIONS: VFH is an infrequent phonotraumatic condition. More studies are needed to advance in knowledge of this pathology as there is contradictory evidence in the literature regarding predisposing factors, evolution and prognosis of this condition.

A papillary fibroelastoma with myxoma camouflage: a case report.

Background: Benign cardiac tumours are infrequent in clinical practice and, of these, cardiac myxoma is the one with the highest incidence. Given that a left intraventricular presentation is rare, other differential diagnoses such as papillary fibroelastoma should be considered. Case summary: A 73-year-old woman patient with cardiac mass detected in transthoracic echocardiography (TTE) after a transient ischaemic attack. At TTE 2D-3D, a left intraventricular mass anchored at the level of the anterolateral papillary muscle was detected. Subsequently, cardiac magnetic resonance (CMR) was performed for mass characterization. This revealed behaviour in T1 (isointense with respect to myocardium), T2 (hyperintense), very prolonged T1-mapping (1848 msg), and T2-mapping (161 msg) values, without gadolinium uptake in the first-pass perfusion sequence, but with intense uptake in late enhancement sequences. Previous findings were compatible with a diagnosis of papillary fibroelastoma. The mass was resected intraoperatively and, although its macroscopic appearance pointed to a diagnosis of cardiac myxoma, it was finally confirmed to be a papillary fibroelastoma by pathological anatomy. Discussion: In cases where the size of the mass and its mobility allow tissue characterization by CMR, a diagnosis of papillary fibroelastoma and its differentiation with cardiac myxoma are feasible by this cardiac imaging technique.

Inteligencia artificial explicable, una perspectiva al problema de la clasificación automática de COVID-19 mediante radiografías de tórax

RESUMEN Esta investigación pretende dilucidar, a partir del análisis de técnicas de inteligencia artificial explicables, la robustez y el nivel de generalización de los métodos de visión por computadora propuestos para identificar COVID-19 utilizando imágenes de radiografías de tórax. Asimismo, alertar a los investigadores y revisores sobre el problema del aprendizaje por atajos. En este estudio se siguen recomendaciones para identificar si los modelos de clasificación automática de COVID-19 se ven afectados por el aprendizaje por atajos. Para ello, se revisaron los artículos que utilizan métodos de inteligencia artificial explicable en dicha tarea. Se evidenció que al utilizar la imagen de radiografía de tórax completa o el cuadro delimitador de los pulmones, las regiones de la imagen que más contribuyen a la clasificación aparecen fuera de la región pulmonar, algo que no tiene sentido. Los resultados indican que, hasta ahora, los modelos existentes presentan el problema de aprendizaje por atajos, lo cual los hace inapropiados para ser usados en entornos clínicos.

ABSTRACT This research aims to elucidate, from the analysis of explainable artificial intelligence techniques, the robustness and level of generalization of the proposed computer vision methods to identify COVID-19 using chest X-ray images. Also, alert researchers and reviewers about the problem of learning by shortcuts. In this study, recommendations are followed to identify if the automatic classification models of COVID-19 are affected by shortcut learning. To do this, articles that use explainable artificial intelligence methods were reviewed. It was shown that when using the full chest X-ray image or the bounding box of the lungs, the regions of the image that contribute the most to the classification appear outside the lung region, something that does not make sense. The results indicate that, so far, the existing models present the problem of learning by shortcuts, which makes them inappropriate to be used in clinical settings.

Caracterización clínica y sociodemográfica de mujeres embarazadas con COVID-19 hospitalizadas / Clinical and sociodemographic characterization of pregnant women hospitalized with COVID-19

Resumen Introducción: En las mujeres embarazadas se identifica mayor riesgo de desarrollar infecciones respiratorias virales. Objetivo: Analizar características sociodemográficas, evolución, manifestaciones clínicas y complicaciones en mujeres embarazadas con COVID-19 que fueron hospitalizadas. Métodos: Estudio en 11 hospitales públicos; se incluyeron variables sociodemográficas, comorbilidades, síntomas y signos, hallazgos de laboratorio y gabinete, características del embarazo, tratamiento y desenlace de la gestación. Resultados: La edad osciló entre 15 y 40 años; 85.1 % cursaba el tercer trimestre del embarazo, 11.9 % el segundo y 3 % el primero; 27 % presentó alguna comorbilidad como obesidad, hipertensión o asma; 89.5 % presentó fiebre, 73.1 % tos, 44.8 % disnea, 43.3 % cefalea y 35.8 % mialgias. Los diagnósticos fueron enfermedad leve (55.2 %), neumonía leve (26.9 %), neumonía severa (10.4 %), neumonía severa con síndrome de distrés respiratorio agudo (4.5 %) y neumonía severa con choque séptico (3 %); 76.2 % recibió soporte de oxígeno no invasivo y 9 %, ventilación mecánica. Se interrumpió el embarazo en 53.8 %; 95.5 % egresó por mejoría y 4.5 % falleció. Conclusiones: El rango de edad y los síntomas coinciden con los señalados en la literatura especializada. En mujeres con COVID-19 se evidenció el incremento de la operación cesárea sin una indicación clara.

Abstract Introduction: In pregnant women, a higher risk for developing viral respiratory infections is identified. Objective: To analyze sociodemographic characteristics, evolution, clinical manifestations, and complications of pregnant women hospitalized with COVID-19. Methods: Study conducted at 11 public hospitals; sociodemographic variables, comorbidities, signs and symptoms, laboratory and imaging findings, pregnancy characteristics, treatment and pregnancy outcome were included for analysis. Results: Age ranged between 15 and 40 years; 85.1% were at third trimester of pregnancy, 11.9% at second and 3% at first; 27% had any comorbidity such as obesity, hypertension or asthma; 89.5% had fever, 73.1% cough, 44.8% dyspnea, 43.3% headache and 35.8% myalgia. Diagnoses were mild disease (55.2%), mild pneumonia (26.9%), severe pneumonia (10.4%), severe pneumonia with acute respiratory distress syndrome (4.5%), and severe pneumonia with septic shock (3%); 76.2% had noninvasive oxygen support, and 9%, mechanical ventilation. Pregnancy was interrupted in 53.8%; 95.5% were discharged due to improvement of their condition and 4.5% died. Conclusions: Age range and symptoms are consistent with those previously reported. Evidence was found of an increase in cesarean section without a clear indication in women with COVID-19.

Screening of CNVs using NGS data improves mutation detection yield and decreases costs in genetic testing for hereditary cancer.

INTRODUCTION: Germline CNVs are important contributors to hereditary cancer. In genetic diagnostics, multiplex ligation-dependent probe amplification (MLPA) is commonly used to identify them. However, MLPA is time-consuming and expensive if applied to many genes, hence many routine laboratories test only a subset of genes of interest. METHODS AND RESULTS: We evaluated a next-generation sequencing (NGS)-based CNV detection tool (DECoN) as first-tier screening to decrease costs and turnaround time and expand CNV analysis to all genes of clinical interest in our diagnostics routine. We used DECoN in a retrospective cohort of 1860 patients where a limited number of genes were previously analysed by MLPA, and in a prospective cohort of 2041 patients, without MLPA analysis. In the retrospective cohort, 6 new CNVs were identified and confirmed by MLPA. In the prospective cohort, 19 CNVs were identified and confirmed by MLPA, 8 of these would have been lost in our previous MLPA-restricted detection strategy. Also, the number of genes tested by MLPA across all samples decreased by 93.0% in the prospective cohort. CONCLUSION: Including an in silico germline NGS CNV detection tool improved our genetic diagnostics strategy in hereditary cancer, both increasing the number of CNVs detected and reducing turnaround time and costs.

Paired Somatic-Germline Testing of 15 Polyposis and Colorectal Cancer-Predisposing Genes Highlights the Role of APC Mosaicism in de Novo Familial Adenomatous Polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome responsible for 1% of colorectal cancers (CRCs). Up to 90% of classic FAPs are caused by inactivating mutations in APC, and mosaicism has been previously reported in 20% of de novo cases, usually linked to milder phenotypic manifestations. This study aimed to explore the prevalence of mosaicism in 11 unsolved cases of classic FAP and to evaluate the diagnostic yield of somatic testing. Paired samples of colorectal polyps, tumors, and/or mucosa were analyzed using a custom next-generation sequencing panel targeting 15 polyposis and CRC-predisposing genes. Whenever possible, the extension of mosaicism to blood or sperm was also examined. Of 11 patients with classic adenomatous polyposis, a mosaic pathogenic variant in APC was identified in 7 (64%). No other altered genes were identified. In two of seven patients (29%), mosaicism was found restricted to colonic tissues, whereas in five of seven patients (71%), it was extended to the blood. Germline affectation was confirmed in one patient. We report the first analysis at a somatic level of 15 genes associated with CRC susceptibility, which highlights the role of APC mosaicism in classic FAP etiology. The results further reinforce the importance of testing target tissues when blood test results are negative.

Leishmania spp Epitopes in Humans Naturally Resistant to the Disease: Working Toward a Synthetic Vaccine.

Vaccines are one of the most effective strategies to fight infectious diseases. Reverse vaccinology strategies provide tools to perform in silico screening and a rational selection of potential candidates on a large scale before reaching in vitro and in vivo evaluations. Leishmania infection in humans produces clinical symptoms in some individuals, while another part of the population is naturally resistant (asymptomatic course) to the disease, and therefore their immune response controls parasite replication. By the identification of epitopes directly in humans, especially in those resistant to the disease, the probabilities of designing an effective vaccine are higher. The aim of this work was the identification of Leishmania epitopes in resistant humans. To achieve that, 11 peptide sequences (from Leishmania antigenic proteins) were selected using epitope prediction tools, and then, peripheral blood mononuclear cells (PBMCs) were isolated from human volunteers who were previously divided into four clinical groups: susceptible, resistant, exposed and not exposed to the parasite. The induction of inflammatory cytokines and lymphoproliferation was assessed using monocyte-derived dendritic cells (moDCs) as antigen-presenting cells (APCs). The response was evaluated after exposing volunteers' cells to each peptide. As a result, we learned that STI41 and STI46 peptides induced IL-8 and IL-12 in moDCs and lymphoproliferation and low levels of IL-10 in lymphocytes differentially in resistant volunteers, similar behavior to that observed in those individuals to L. panamensis lysate antigens. We conclude that, in silico analysis allowed for the identification of natural Leishmania epitopes in humans, and also STI41 and STI46 peptides could be epitopes that lead to a cellular immune response directed at parasite control.

BARD1 Pathogenic Variants are Associated with Triple-Negative Breast Cancer in a Spanish Hereditary Breast and Ovarian Cancer Cohort.

Only a small fraction of hereditary breast and/or ovarian cancer (HBOC) cases are caused by germline variants in the high-penetrance breast cancer 1 and 2 genes (BRCA1 and BRCA2). BRCA1-associated ring domain 1 (BARD1), nuclear partner of BRCA1, has been suggested as a potential HBOC risk gene, although its prevalence and penetrance are variable according to populations and type of tumor. We aimed to investigate the prevalence of BARD1 truncating variants in a cohort of patients with clinical suspicion of HBOC. A comprehensive BARD1 screening by multigene panel analysis was performed in 4015 unrelated patients according to our regional guidelines for genetic testing in hereditary cancer. In addition, 51,202 Genome Aggregation Database (gnomAD) non-Finnish, non-cancer European individuals were used as a control population. In our patient cohort, we identified 19 patients with heterozygous BARD1 truncating variants (0.47%), whereas the frequency observed in the gnomAD controls was 0.12%. We found a statistically significant association of truncating BARD1 variants with overall risk (odds ratio (OR) = 3.78; CI = 2.10-6.48; p = 1.16 × 10-5). This association remained significant in the hereditary breast cancer (HBC) group (OR = 4.18; CI = 2.10-7.70; p = 5.45 × 10-5). Furthermore, deleterious BARD1 variants were enriched among triple-negative BC patients (OR = 5.40; CI = 1.77-18.15; p = 0.001) compared to other BC subtypes. Our results support the role of BARD1 as a moderate penetrance BC predisposing gene and highlight a stronger association with triple-negative tumors.

Manejo de las crisis glucémicas en pacientes adultos con diabetes mellitus: Guía de práctica clínica basada en evidencias

Introducción: El artículo resume el proceso de elaboración de la Guía de Práctica Clínica (GPC) para el manejo de las crisis glucémicas en pacientes adultos con diabetes mellitus de la Red de Clínicas AUNA. Métodos: Las preguntas PICO fueron priorizadas por el Grupo Elaborador de la GPC (GEG) luego de lo cual se concluyó en trabajar 10 preguntas PICO. Para dar respuesta a las preguntas se realizó una búsqueda sistemática de GPC, revisiones sistemáticas y estudios primarios. Se utilizó la metodología "GRADE-Adolopment" y los lineamientos de la normativa nacional para la formulación de recomendaciones. Resultados: Se formularon 10 recomendaciones (nueve fuertes y una débil), 18 puntos de buena práctica clínica, dos flujogramas para el manejo (uno para el diagnóstico y el otro para el tratamiento de crisis glucémicas), 5 tablas resumen sobre el manejo y 1 tabla para la vigilancia y seguimiento. Los temas que abarcaron las recomendaciones para el manejo de las crisis glucémicas fueron: crisis hiperglucémicas (evaluación de hemoglobina glucosilada; evaluación de b-hidroxibutirato; tratamiento con insulina, potasio, cloruro de sodio 0.9%, fósforo y bicarbonato de sodio) y crisis hipoglucémicas (administración de carbohidratos, monitoreo y programa educativo para evitar el reingreso). Conclusión: El presente artículo resume la metodología y las recomendaciones basadas en evidencia de la GPC para el manejo de la crisis glucémica en pacientes con diabetes mellitus de la Red de Clínicas AUNA.

Introduction: The manuscript summarizes the process of elaboration of the Clinical Practice Guide (CPG) for the management of glycemic crises in adult patients with diabetes mellitus of the AUNA Clinic Network. A multidisciplinary team of medical assistants and methodologists carried out the development of the CPG and then there was an external review by a specialist in the field. Methods: The Elaboration Group of the CPG (GEG) concluded on 10 PICO questions. A systematic search for CPG, systematic reviews and primary studies was carried out to answer these PICO questions. To make recommendations we used the "GRADE-Adolopment" methodology and the guidelines of the national regulations. Results: Ten recommendations were made (nine strong and one weak), 18 points of good clinical practice and two flowcharts for management (one for diagnosis and the other for the treatment of glycemic crises), 04 consensus tables on management and 01 table for surveillance and monitoring. The topics covered by the recommendations for the management of glycemic crises were hyperglycemic crises (glycosylated hemoglobin evaluation; b-hydroxybutyrate evaluation; insulin, potassium, 0.9% sodium chloride, phosphorus, sodium bicarbonate treatments) and hypoglycemic crises (carbohydrate administration, monitoring, educational program to avoid reentry). Conclusion: This article summarizes the methodology and evidence-based recommendations of the CPG for the management of glycemic crisis in patients with diabetes mellitus in AUNA.

Manejo De Las Crisis Glucémicas En Pacientes Adultos Con Diabetes Mellitus: Guía De Práctica Clínica Basada En Evidencia, Lima - Perú / Management of glycemic crises in adult patients with diabetes mellitus: Evidence-based Clinical Practice Guideline, Lima - Peru

The manuscript summarizes the process of elaboration of the Clinical Practice Guide (CPG) for the management of glycemic crises in adult patients with diabetes mellitus of the AUNA Clinic Network. A multidisciplinary team of medical assistants and methodologists carried out the development of the CPG and then there was an external review by a specialist in the field. The Elaboration Group of the CPG (GEG) concluded on 10 PICO questions. A systematic search for CPG, systematic reviews and primary studies was carried out to answer these PICO questions. To make recommendations we used the "GRADE-Adolopment" methodology and the guidelines of the national regulations. Ten recommendations were made (nine strong and one weak), 18 points of good clinical practice and two flowcharts for management (one for diagnosis and the other for the treatment of glycemic crises), 04 consensus tables on management and 01 table for surveillance and monitoring. The topics covered by the recommendations for the management of glycemic crises were hyperglycemic crises (glycosylated hemoglobin evaluation; b-hydroxybutyrate evaluation; insulin, potassium, 0.9% sodium chloride, phosphorus, sodium bicarbonate treatments) and hypoglycemic crises (carbohydrate administration, monitoring, educational program to avoid reentry)

El artículo resume el proceso de elaboración de la Guía de Práctica Clínica (GPC) para el manejo de las crisis glucémicas en pacientes adultos con diabetes mellitus de la Red de Clínicas AUNA. El proceso de elaboración se llevó a cabo con la participación de un equipo multidisciplinario de médicos asistenciales, metodólogos y un revisor externo (un especialista con dominio en la metodología y el tema). La priorización de preguntas PICO fue realizada por el Grupo Elaborador de la GPC (GEG) luego de lo cual se concluyó en trabajar 10 preguntas PICO. Para dar respuesta a las preguntas se realizó una búsqueda sistemática de GPC, revisiones sistemáticas y estudios primarios. Se utilizó la metodología "GRADE-Adolopment" y los lineamientos de la normativa nacional para la formulación de recomendaciones. Se formularon 10 recomendaciones (nueve fuertes y una débil), 18 puntos de buena práctica clínica, dos flujogramas para el manejo (uno para el diagnóstico y el otro para el tratamiento de crisis glucémicas), cinco (05) tablas resumen sobre el manejo y una (01) tabla para la vigilancia y seguimiento. Los temas que abarcaron las recomendaciones para el manejo de las crisis glucémicas fueron: crisis hiperglucémicas (evaluación de hemoglobina glucosilada; evaluación de b-hidroxibutirato; tratamiento con insulina, potasio, cloruro de sodio 0.9%, fósforo, bicarbonato de sodio) y crisis hipoglucémicas (administración de carbohidratos, monitoreo, programa educativo para evitar el reingreso).